Automated collection and analysis patient care system and method for diagnosing and monitoring the outcomes of atrial fibrillation

ABSTRACT

An automated system and method for diagnosing and monitoring the outcomes of atrial fibrillation is described. A plurality of monitoring sets is retrieved from a database. Each of the monitoring sets include recorded measures relating to patient information recorded on a substantially continuous basis. A patient status change is determined in response to an atrial fibrillation diagnosis by comparing at least one recorded measure from each of the monitoring sets to at least one other recorded measure. Both recorded measures relate to the same type of patient information. Each patient status change is tested against an indicator threshold corresponding to the same type of patient information as the recorded measures which were compared. The indicator threshold corresponds to a quantifiable physiological measure of a pathophysiology resulting from atrial fibrillation.

CROSS REFERENCE TO RELATED APPLICATION

This patent application is related to a commonly owned U.S. patentapplication, Serial No. 09/441,405, entitled “Automated Collection AndAnalysis Patient Care System And Method For Ordering And PrioritizingMultiple Health Disorders To Identify An Index Disorder,” pending, filedNov. 16, 1999, the disclosure of which is incorporated herein byreference.

FIELD OF THE INVENTION

The present invention relates in general to atrial fibrillation (AF)diagnosis and analysis, and, in particular, to an automated collectionand analysis patient care system and method for diagnosing andmonitoring the outcomes, including cardiovascular consequences, ofatrial fibrillation throughout disease onset, progression, regressionand status quo.

BACKGROUND OF THE INVENTION

Atrial fibrillation is a heart rhythm abnormality that is one of theleading causes of cardiovascular disease-related morbidity in the world.Clinically, atrial fibrillation involves an abnormality of electricalimpulse formation and conduction that originates in the atria, that is,the upper chambers of the heart. Atrial fibrillation can occur inpatients with any type of underlying structural heart abnormality, suchas coronary artery disease, valvular heart disease, congenital heartdisease, and cardiomyopathies of various kinds, thereby complicatingpatient management and therapy. Further, atrial fibrillation cansometimes occur in patients with no known underlying structuralabnormalities or in patients with lung disease or hormonal or metabolicdisorders. As well, the occurrence of atrial fibrillation can exacerbateother disorders, for example, myocardial ischemia or congestive heartfailure. Effective treatment must include weighing the presence of anycomorbidities primary or secondary to atrial fibrillation and whethertherapy should be directed against rate control or restoration of normalsinus rhythm.

Atrial fibrillation is characterized by multiple swirling wavelets ofelectrical current spreading across the atria in a disorganized manner.The irregularity of electrical conduction throughout the atria createsirregular impulse propagation through the atrioventricular node into theventricle and can frequently cause a patient to notice a disturbinglyerratic sensation of the heartbeat. These symptoms of an erraticheartbeat, or palpitation, can be trivial or seriously disturbing to thepatient's daily functions. Occasionally, the impulse conduction isextremely rapid, leading to reduced diastolic filling of the heartchambers and reduced cardiac pumping action. Rapid heart rate, as wellas poor coordination of atrial and ventricular pumping functions, notonly lead to a decrease in cardiac output, but also, depending upon thenature of any underlying heart disease, can exacerbate heart failure,coronary blood flow, and pulmonary disorders. Atrial fibrillation mayalso occur and be totally inconsequential in its cardiovascular andcardiopulmonary consequences or its affect on the patient's quality oflife. Yet, even if silent from a cardiovascular and symptom perspective,if persisting beyond a 48 hour period, atrial fibrillation can alsoresult in blood clot formation in the atria, thereby creating thepotential for thromboembolism which can lead to strokes or injuries tolimbs and major organs. Thus, the outcomes or consequences of atrialfibrillation can be gross or subtle and be rapid or gradual in onset,consequently requiring a range of approaches, from observation toproviding emergent interventions.

The early diagnosis, prevention and monitoring of the consequences ofatrial fibrillation can be relatively difficult. First, atrialfibrillation onset runs an erratic, unpredictable course and isgenerally silent and undetectable to the patient. More often, atrialfibrillation either results in no symptoms at least for some period oftime early in the course of onset, or in fatigue or difficulties inbreathing usually in the case of those patients having comorbidconditions. Occasionally, a patient will have no complaints but willunconsciously compensate by limiting his or her daily activities.Sometimes, the consequences of atrial fibrillation are more overt. Inany case, fatigue or difficulty breathing is often a consequence ofatrial fibrillation complicating the pathophysiology of coexistingconditions of congestive heart failure, myocardial ischemia, and/orrespiratory insufficiency, for example.

The susceptibility to suffer from atrial fibrillation depends upon thepatient's age, gender, physical condition, presence or absence of heartfailure, coronary artery disease, lung disease, and the incidence ofother factors, such as diabetes, lung disease, high blood pressure,anemia and kidney function. No one factor is dispositive. Evaluationsfor atrial fibrillation and its consequences, with annual or evenmonthly checkups, provide, at best, a “snapshot” of patient wellness andthe incremental and subtle clinicophysiological changes which portendthe onset or progression of atrial fibrillation often go unnoticed,unless electrocardiographic documentation is obtained and simultaneouslycorrelated with cardiovascular and cardiopulmonary physiologicalmeasures. Documentation of improvements following initiation of therapycan be equally elusive.

Nevertheless, taking advantage of frequently and regularly measuredphysiological measures, such as recorded manually by a patient, via anexternal monitoring or therapeutic device, or via implantable devicetechnologies, can provide a degree of detection, treatment andprevention heretofore unknown. In addition, monitoring of thephysiological consequences of the onset and offset of atrialfibrillation can provide invaluable guidance in directing when and whattherapeutic intervention is most appropriate, particularly when atrialfibrillation is coupled with other comorbidities. For instance, patientsalready suffering from some form of treatable heart disease oftenreceive an implantable pulse generator (IPG), cardiovascular orarrhythmia monitor, therapeutic device, or similar external wearabledevice, with which rhythm and structural problems of the heart can bemonitored and treated. These types of devices are useful for detectingphysiological changes in patient conditions through the retrieval andanalysis of telemetered signals stored in an on-board, volatile memory.Typically, these devices can store more than thirty minutes of perheartbeat data recorded on a per heartbeat, binned average basis, or ona derived basis from, for example, extensive data regarding atrial orventricular electrical activity, minute ventilation, patient activityscore, cardiac output score, mixed venous oxygen score, cardiovascularpressure measures, and the like. However, the proper analysis ofretrieved telemetered signals requires detailed medical subspecialtyknowledge, particularly by cardiologists and cardiacelectrophysiologists.

Alternatively, these telemetered signals can be remotely collected andanalyzed using an automated patient care system. One such system isdescribed in a related, commonly owned U.S. patent application, Ser. No.09/324,894, filed Jun. 3, 1999, pending, the disclosure of which isincorporated herein by reference. A medical device adapted to beimplanted in an individual patient records telemetered signals that arethen retrieved on a regular, periodic basis using an interrogator orsimilar interfacing device. The telemetered signals are downloaded viaan internetwork onto a network server on a regular, e.g., daily, basisand stored as sets of collected measures in a database along with otherpatient care records. The information is then analyzed in an automatedfashion and feedback, which includes a patient status indicator, isprovided to the patient.

While such an automated system can serve as a valuable tool in providingremote patient care, an approach to systematically correlating andanalyzing the raw collected telemetered signals, as well as manuallycollected physiological measures, through applied cardiovascular medicalknowledge to accurately diagnose the consequences of the onset of aparticular medical condition, such as atrial fibrillation, is needed.One automated patient care system directed to a patient-specificmonitoring function, albeit focused on ventricular rather than atrialarrhythmias, is described in U.S. Pat. No. 5,113,869 ('869) to Nappholzet al. The '869 patent discloses an implantable, programmableelectrocardiography (ECG) patient monitoring device that senses andanalyzes ECG signals to detect ECG and physiological signalcharacteristics predictive of malignant cardiac arrhythmias. Themonitoring device can communicate a warning signal to an external devicewhen arrhythmias are predicted. However, the Nappholz device is limitedto detecting tachycardias. Unlike requirements for automated monitoringof the consequences of atrial fibrillation, the Nappholz device focuseson rudimentary ECG signals indicative of malignant cardiac tachycardias,an already well-established technique that can be readily used withon-board signal detection techniques. Also, the Nappholz device ispatient specific only and is unable to automatically take intoconsideration a broader patient or peer group history for reference todetect and consider the progression or improvement of cardiovasculardisease. Moreover, the Nappholz device has a limited capability toautomatically self-reference multiple data points in time and cannotdetect disease regression even in the individual patient. In addition,the Nappholz device must be implanted and cannot function as an externalmonitor. Also, the Nappholz device neither monitors nor treats thecardiovascular and cardiopulmonary consequences of atrial fibrillation.

More specifically, the diagnosis and treatment of atrial fibrillationusing implantable anti-arrhythmia devices has been widely addressed inthe prior art and is described, for example, in U.S. Pat. No. 5,931,857('857) to Prieve et al. and U.S. Pat. No. 5,855,593 ('593) to Olson etal. The '857 patent discloses an implantable device which continuouslymonitors for tachyarrhythmia conditions and an associated patientactivator. Two sets of arrhythmia detection criteria are utilized forevaluating autonomous and patient-activated anti-arrhythmia therapy. The'593 patent discloses a device capable of arrhythmia detection andclassification based on a set of prioritized rules. However, both thePrieve and Olson devices are directed to diagnosing and treating thearrhythmias in isolation without detailed consideration of coexistingconditions and the cardiovascular and cardiopulmonary consequences ofthose disorders.

As a result, there is a need for a systematic approach to detectingtrends in regularly collected physiological data indicative of theonset, progression, regression, or status quo of atrial fibrillationdiagnosed and monitored using an automated, remote patient care system,such need being particularly heightened in the presence ofcomorbidities, such as congestive heart failure, myocardial ischemia,respiratory insufficiency, and related disorders. The physiological datacould be telemetered signals data recorded either by an external or animplantable medical device or, alternatively, individual measurescollected through manual means. Preferably, such an approach would becapable of diagnosing the cardiovascular and cardiopulmonaryconsequences of both acute and chronic atrial fibrillation conditions,as well as the symptoms of other cardiovascular diseases. In addition,findings from individual, peer group, and general population patientcare records could be integrated into continuous, on-going monitoringand analysis.

SUMMARY OF THE INVENTION

The present invention provides a system and method for diagnosing andmonitoring the consequences of the onset, progression, regression, andstatus quo of atrial fibrillation and its related pathophysiological,especially cardiovascular and cardiopulmonary, consequences using anautomated collection and analysis patient care system. Measures ofpatient cardiovascular information are either recorded by an external orimplantable medical device, such as an IPG, cardiovascular or heartfailure monitor, or therapeutic device, or manually through conventionalpatient-operable means. The measures are collected on a regular,periodic basis for storage in a database along with other patient carerecords. Derived measures are developed from the stored measures. Selectstored and derived measures are analyzed and changes in patientcondition are logged. The logged changes are compared to quantifiedindicator thresholds to detect findings of reduced exercise capacity,respiratory distress, or other symptoms, including palpitations,indicative of the principal cardiovascular pathophysiologicalmanifestations of atrial fibrillation.

An embodiment of the present invention is an automated system and methodfor diagnosing and monitoring the outcomes, including cardiovascular andcardiopulmonary consequences, of atrial fibrillation. A plurality ofmonitoring sets is retrieved from a database. Each of the monitoringsets includes recorded measures relating to patient information recordedon a substantially continuous basis. A patient status change isdetermined in response to an atrial fibrillation diagnosis by comparingat least one recorded measure from each of the monitoring sets to atleast one other recorded measure. Both recorded measures relate to thesame type of patient information. Each patient status change is testedagainst an indicator threshold corresponding to the same type of patientinformation as the recorded measures that were compared. The indicatorthreshold corresponds to a quantifiable physiological measure of apathophysiology resulting from atrial fibrillation.

A further embodiment is an automated collection and analysis patientcare system and method for diagnosing and monitoring the outcomes ofatrial fibrillation. A plurality of monitoring sets is retrieved from adatabase. Each monitoring set includes recorded measures that eachrelates to patient information and include either medical devicemeasures or derived measures calculable therefrom. The medical devicemeasures are recorded on a substantially continuous basis. A set ofindicator thresholds is defined. Each indicator threshold corresponds toa quantifiable physiological measure of a pathophysiology resulting fromatrial fibrillation and relates to the same type of patient informationas at least one of the recorded measures. A change in patient status isdetermined in response to an atrial fibrillation diagnosis by comparingat least one recorded measure to at least one other recorded measurewith both recorded measures relating to the same type of patientinformation. Each patient status change is compared to the indicatorthreshold corresponding to the same type of patient information as therecorded measures that were compared.

A further embodiment is an automated patient care system for diagnosingand monitoring the outcomes of atrial fibrillation and method thereof.Recorded measures organized into a monitoring set for an individualpatient are stored into a database. Each recorded measure is recorded ona substantially continuous basis and relates to at least one aspect ofmonitoring reduced exercise capacity, respiratory distress, andpalpitations/symptoms. A plurality of the monitoring sets isperiodically retrieved from the database. At least one measure relatedto the onset, progression, regression, and status quo of atrialfibrillation and its consequences is evaluated. A patient status changeis determined in response to an atrial fibrillation diagnosis bycomparing at least one recorded measure from each of the monitoring setsto at least one other recorded measure with both recorded measuresrelating to the same type of patient information. Each patient statuschange is tested against an indicator threshold corresponding to thesame type of patient information as the recorded measures that werecompared. The indicator threshold corresponds to a quantifiablephysiological measure of a pathophysiology indicative of reducedexercise capacity, respiratory distress, palpitations, syncope,near-syncope or other cardiovascular consequences of atrialfibrillation.

A further embodiment is an automated system and method for managing apathophysiological outcome of atrial fibrillation. A plurality ofmonitoring sets is retrieved from a database. Each monitoring setincludes recorded measures relating to patient information recorded on asubstantially continuous basis. Atrial fibrillation is diagnosed. Apathophysiological outcome of atrial fibrillation is determined inresponse to the atrial fibrillation diagnosis. At least one recordedmeasure from each of the monitoring sets is compared to at least oneother recorded measure with both recorded measures relating to the sametype of patient information. Each recorded measure comparison is testedagainst an indicator threshold corresponding to the same type of patientinformation as the recorded measures which were compared. The indicatorthreshold corresponds to a quantifiable physiological measure of apathophysiology resulting from atrial fibrillation. The atrialfibrillation outcome is managed through interventive administration oftherapy contributing to normal sinus rhythm restoration and ventricularrate response control.

The present invention provides a capability to detect and track subtletrends and incremental changes in recorded patient information fordiagnosing and monitoring the outcomes of atrial fibrillation. Whencoupled with an enrollment in a remote patient monitoring service havingthe capability to remotely and continuously collect and analyze externalor implantable medical device measures, atrial fibrillation detection,prevention and tracking regression from therapeutic maneuvers becomefeasible.

Still other embodiments of the present invention will become readilyapparent to those skilled in the art from the following detaileddescription, wherein is described embodiments of the invention by way ofillustrating the best mode contemplated for carrying out the invention.As will be realized, the invention is capable of other and differentembodiments and its several details are capable of modifications invarious obvious respects, all without departing from the spirit and thescope of the present invention. Accordingly, the drawings and detaileddescription are to be regarded as illustrative in nature and not asrestrictive.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram showing an automated collection and analysispatient care system for diagnosing and monitoring the outcomes of atrialfibrillation in accordance with the present invention;

FIG. 2 is a database schema showing, by way of example, the organizationof a device and derived measures set record for care of patients withatrial fibrillation stored as part of a patient care record in thedatabase of the system of FIG. 1;

FIG. 3 is a database schema showing, by way of example, the organizationof a quality of life and symptom measures set record for care ofpatients with atrial fibrillation stored as part of a patient carerecord in the database of the system of FIG. 1;

FIG. 4 is a database schema showing, by way of example, the organizationof a combined measures set record for care of patients with atrialfibrillation stored as part of a patient care record in the database ofthe system of FIG. 1;

FIG. 5 is a block diagram showing the software modules of the serversystem of the system of FIG. 1;

FIG. 6 is a record view showing, by way of example, a set of partialpatient care records for care of patients with atrial fibrillationstored in the database of the system of FIG. 1;

FIG. 7 is a Venn diagram showing, by way of example, peer group overlapbetween the partial patient care records of FIG. 6;

FIGS. 8A-8B are flow diagrams showing a method for diagnosing andmonitoring the outcomes of atrial fibrillation using an automatedcollection and analysis patient care system in accordance with thepresent invention;

FIG. 9 is a flow diagram showing the routine for retrieving referencebaseline sets for use in the method of FIGS. 8A-8B;

FIG. 10 is a flow diagram showing the routine for retrieving monitoringsets for use in the method of FIGS. 8A-8B;

FIGS. 11A-11D are flow diagrams showing the routine for testingthreshold limits for use in the method of FIGS. 8A-8B;

FIGS. 12A-12B are flow diagrams showing the routine for evaluating theconsequences of the onset, progression, regression, and status quoassociated with atrial fibrillation for use in the method of FIGS.8A-8B;

FIGS. 13A-13B are flow diagrams showing the routine for categorizing anonset of atrial fibrillation for use in the routine of FIGS. 12A-12B;

FIGS. 14A-14B are flow diagrams showing the routine for categorizing aprogression or worsening of atrial fibrillation for use in the routineof FIGS. 12A-12B;

FIGS. 15A-15B are flow diagrams showing the routine for categorizing aregression or improving of atrial fibrillation 227 and itscardiovascular and cardiopulmonary consequences for use in the routineof FIGS. 12A-12B;

FIG. 16 is a flow diagram showing the routine for determining thresholdstickiness (“hysteresis”) for use in the method of FIGS. 12A-12B;

FIGS. 17A-17B is a flow diagram showing the routine for managing theconsequences of atrial fibrillation for use in the routine of FIGS.12A-12B;

FIGS. 18A-18D are flow diagrams showing the routine for managing acardiovascular/cardiopulmonary compromise for use in the method of FIGS.17A-17B;

FIG. 19 is a flow diagram showing the routine for managing ventricularrate response for use in the method of FIGS. 17A-17B;

FIG. 20 is a flow diagram showing the routine for managinganticoagulation for use in the method of FIGS. 17A-17B; and

FIG. 21 is a flow diagram showing the routine for managing palpitationsfor use in the method of FIGS. 17A-17B.

DETAILED DESCRIPTION

FIG. 1 is a block diagram showing an automated collection and analysispatient care system 10 for diagnosing and monitoring the outcomes ofatrial fibrillation in accordance with the present invention. Anexemplary automated collection and analysis patient care system suitablefor use with the present invention is disclosed in the related,commonly-owned U.S. patent application, Ser. No. 09/324,894, pending,filed Jun. 3, 1999, the disclosure of which is incorporated herein byreference. Preferably, an individual patient 11 is a recipient of animplantable medical device 12, such as, by way of example, an IPG,cardiovascular or heart failure monitor, or therapeutic device, with aset of leads extending into his or her heart and electrodes implantedthroughout the cardiopulmonary system. In the described embodiment, animplantable anti-arrhythmia device capable of diagnosing and treatingarrhythmias can be used, such as disclosed in U.S. Pat. No. 5,931,857 toPrieve et al. and U.S. Pat. No. 5,855,593 to Olson et al. Alternatively,an external monitoring or therapeutic medical device 26, a subcutaneousmonitor or device inserted into other organs, a cutaneous monitor, oreven a manual physiological measurement device, such as anelectrocardiogram or heart rate monitor, could be used. The implantablemedical device 12 and external medical device 26 include circuitry forrecording into a short-term, volatile memory telemetered signals storedfor later retrieval, which become part of a set of device and derivedmeasures, such as described below, by way of example, with reference toFIG. 2. Exemplary implantable medical devices suitable for use in thepresent invention include the Discovery line of pacemakers, manufacturedby Guidant Corporation, Indianapolis, Ind., and the Gem line of ICDs,manufactured by Medtronic Corporation, Minneapolis, Minn.

The telemetered signals stored in the implantable medical device 12 arepreferably retrieved upon the completion of an initial observationperiod and subsequently thereafter on a continuous, periodic (daily)basis, such as described in the related, commonly-owned U.S. patentapplication, Ser. No. 09/361,332, pending, filed Jul. 26, 1999, thedisclosure of which is incorporated herein by reference. A programmer14, personal computer 18, or similar device for communicating with animplantable medical device 12 can be used to retrieve the telemeteredsignals. A magnetized reed switch (not shown) within the implantablemedical device 12 closes in response to the placement of a wand 13 overthe site of the implantable medical device 12. The programmer 14 sendsprogramming or interrogating instructions to and retrieves storedtelemetered signals from the implantable medical device 12 via RFsignals exchanged through the wand 13. Similar communication means areused for accessing the external medical device 26. Once downloaded, thetelemetered signals are sent via an internetwork 15, such as theInternet, to a server system 16 which periodically receives and storesthe telemetered signals as device measures in patient care records 23 ina database 17, as further described below, by way of example, withreference to FIGS. 2 and 3. An exemplary programmer 14 suitable for usein the present invention is the Model 2901 Programmer Recorder Monitor,manufactured by Guidant Corporation, Indianapolis, Ind.

The patient 11 is remotely monitored by the server system 16 via theinternetwork 15 through the periodic receipt of the retrieved devicemeasures from the implantable medical device 12 or external medicaldevice 26. The patient care records 23 in the database 17 are organizedinto two identified sets of device measures: an optional referencebaseline 26 recorded during an initial observation period and monitoringsets 27 recorded subsequently thereafter. The device measures sets areperiodically analyzed and compared by the server system 16 to indicatorthresholds corresponding to quantifiable physiological measures of apathophysiology resulting from atrial fibrillation and any relatedcomorbidities, as further described below with reference to FIG. 5. Asnecessary, feedback is provided to the patient 11. By way of example,the feedback includes an electronic mail message automatically sent bythe server system 16 over the internetwork 15 to a personal computer 18(PC) situated for local access by the patient 11. Alternatively, thefeedback can be sent through a telephone interface device 19 as anautomated voice mail message to a telephone 21 or as an automatedfacsimile message to a facsimile machine 22, both also situated forlocal access by the patient 11. Moreover, simultaneous notifications canalso be delivered to the patient's physician, hospital, or emergencymedical services provider 29 using similar feedback means to deliver theinformation. The server system 10 can consist of either a singlecomputer system or a cooperatively networked or clustered set ofcomputer systems. Each computer system is a general purpose, programmeddigital computing device consisting of a central processing unit (CPU),random access memory (RAM), non-volatile secondary storage, such as ahard drive or CD ROM drive, network interfaces, and peripheral devices,including user interfacing means, such as a keyboard and display.Program code, including software programs, and data are loaded into theRAM for execution and processing by the CPU and results are generatedfor display, output, transmittal, or storage, as is known in the art.

The database 17 stores patient care records 23 for each individualpatient to whom remote patient care is being provided. Each patient carerecord 23 contains normal patient identification and treatment profileinformation, as well as medical history, medications taken, height andweight, and other pertinent data (not shown). The patient care records23 consist primarily of two sets of data: device and derived measures(D&DM) sets 24 a, 24 b and quality of life (QOL) and symptom measuressets 25 a, 25 b, the organization of which are further described belowwith respect to FIGS. 2 and 3, respectively. The device and derivedmeasures sets 24 a, 24 b and quality of life and symptom measures sets25 a, 25 b can be further logically categorized into two potentiallyoverlapping sets. The reference baseline 26 is a special set of deviceand derived reference measures sets 24 a and quality of life and symptommeasures sets 25 a recorded and determined during an initial observationperiod. Monitoring sets 27 are device and derived measures sets 24 b andquality of life and symptom measures sets 25 b recorded and determinedthereafter on a regular, continuous basis. Other forms of databaseorganization are feasible.

The implantable medical device 12 and, in a more limited fashion, theexternal medical device 26, record patient information for care ofpatients with atrial fibrillation on a regular basis. The recordedpatient information is downloaded and stored in the database 17 as partof a patient care record 23. Further patient information can be derivedfrom recorded data, as is known in the art. FIG. 2 is a database schemashowing, by way of example, the organization of a device and derivedmeasures set record 40 for patient care stored as part of a patient carerecord in the database 17 of the system of FIG. 1. Each record 40 storespatient information which includes a snapshot of telemetered signalsdata which were recorded by the implantable medical device 12 or theexternal medical device 26, for instance, on per heartbeat, binnedaverage or derived bases; measures derived from the recorded devicemeasures; and manually collected information, such as obtained through apatient medical history interview or questionnaire. The followingnon-exclusive information can be recorded for a patient: atrialelectrical activity 41, ventricular electrical activity 42, PR intervalor AV interval 43, QRS measures 44, ST-T wave measures 45, QT interval46, body temperature 47, patient activity score 48, posture 49,cardiovascular pressures 50, pulmonary artery diastolic pressure measure51, cardiac output 52, systemic blood pressure 53, patient geographiclocation and location (altitude) 54, mixed venous oxygen score 55,arterial oxygen score 56, pulmonary measures 57, minute ventilation 58,potassium [K+] level 59, sodium [Na+] level 60, glucose level 61, bloodurea nitrogen (BUN) and creatinine 62, acidity (pH) level 63, hematocrit64, hormonal levels 65, cardiac injury chemical tests 66, myocardialblood flow 67, central nervous system (CNS) injury chemical tests 68,central nervous system blood flow 69, interventions made by theimplantable medical device or external medical device 70, and therelative success of any interventions made 71. In addition, theimplantable medical device or external medical device communicatesdevice-specific information, including battery status, general devicestatus and program settings 72 and the time of day 73 for the variousrecorded measures. Other types of collected, recorded, combined, orderived measures are possible, as is known in the art.

The device and derived measures sets 24 a, 24 b (shown in FIG. 1), alongwith quality of life and symptom measures sets 25 a, 25 b, as furtherdescribed below with reference to FIG. 3, are continuously andperiodically received by the server system 16 as part of the on-goingpatient care monitoring and analysis function. These regularly collecteddata sets are collectively categorized as the monitoring sets 27 (shownin FIG. 1). In addition, select device and derived measures sets 24 aand quality of life and symptom measures sets 25 a can be designated asa reference baseline 26 at the outset of patient care to improve theaccuracy and meaningfulness of the serial monitoring sets 27. Selectpatient information is collected, recorded, and derived during aninitial period of observation or patient care, such as described in therelated, commonly-owned U.S. patent application, Serial No. 09/ 361,332,pending, filed Jul. 26, 1999, the disclosure of which is incorporatedherein by reference.

As an adjunct to remote patient care through the monitoring of measuredphysiological data via the implantable medical device 12 or externalmedical device 26, quality of life and symptom measures sets 25 a canalso be stored in the database 17 as part of the reference baseline 26,if used, and the monitoring sets 27. A quality of life measure is asemi-quantitative self-assessment of an individual patient's physicaland emotional well-being and a record of symptoms, such as provided bythe Duke Activities Status Indicator. These scoring systems can beprovided for use by the patient 11 on the personal computer 18 (shown inFIG. 1) to record his or her quality of life scores for both initial andperiodic download to the server system 16. FIG. 3 is a database schemashowing, by way of example, the organization of a quality of life record80 for use in the database 17. The following information is recorded fora patient: overall health wellness 81, psychological state 82,activities of daily living 83, work status 84, geographic location 85,family status 86, shortness of breath 87, energy level 88, exercisetolerance 89, chest discomfort 90, palpitations 91, syncope 92, nearsyncope 93, time of day 94, and other quality of life and symptommeasures as would be known to one skilled in the art.

Other types of quality of life and symptom measures are possible, suchas those indicated by responses to the Minnesota Living with HeartFailure Questionnaire described in E. Braunwald, ed., “Heart Disease—ATextbook of Cardiovascular Medicine,” pp. 452-454, W.B. Saunders Co.(1997), the disclosure of which is incorporated herein by reference.Similarly, functional classifications based on the relationship betweensymptoms and the amount of effort required to provoke them can serve asquality of life and symptom measures, such as the New York HeartAssociation (NYHA) classifications I, II, III and IV, also described inIbid.

The patient may also add non-device quantitative measures, such as thesix-minute walk distance, as complementary data to the device andderived measures sets 24 a, 24 b and the symptoms associated with thesix minute walk to the quality of life and symptom measures sets 25 a,25 b.

On a periodic basis, the patient information stored in the database 17is analyzed and compared to pre-determined cutoff levels, which, whenexceeded, can provide etiological indications of atrial fibrillationsymptoms. FIG. 4 is a database schema showing, by way of example, theorganization of a combined measures set record 95 for use in thedatabase 17. Each record 95 stores patient information obtained orderived from the device and derived measures sets 24 a, 24 b and qualityof life and symptom measures sets 25 a, 25 b as maintained in thereference baseline 26, if used, and the monitoring sets 27. The combinedmeasures set 95 represents those measures most (but not exhaustively orexclusively) relevant to a pathophysiology resulting from atrialfibrillation and are determined as further described below withreference to FIGS. 8A-8B. The following information is stored for apatient: heart rate 96, heart rhythm (e.g., normal sinus vs. atrialfibrillation) 97, pacing modality 98, pulmonary artery diastolicpressure 99, cardiac output 100, arterial oxygen score 101, mixed venousoxygen score 102, respiratory rate 103, transthoracic impedance 104,patient activity score 105, posture 106, exercise tolerance quality oflife and symptom measures 107, respiratory distress quality of life andsymptom measures 108, palpitations quality of life measures 109,syncope/near syncope quality of life measures 110, any interventionsmade to treat atrial fibrillation 111, including treatment by medicaldevice, via drug infusion administered by the patient or by a medicaldevice, surgery, and any other form of medical intervention as is knownin the art, the relative success of any such interventions made 112, anddate and time of day 113. Other types of comparison measures regardingatrial fibrillation are possible as is known in the art. In thedescribed embodiment, each combined measures set 95 is sequentiallyretrieved from the database 17 and processed. Alternatively, eachcombined measures set 95 could be stored within a dynamic data structuremaintained transitorily in the random access memory of the server system16 during the analysis and comparison operations. FIG. 5 is a blockdiagram showing the software modules of the server system 16 of thesystem 10 of FIG. 1. Each module is a computer program written as sourcecode in a conventional programming language, such as the C or Javaprogramming languages, and is presented for execution by the CPU of theserver system 16 as object or byte code, as is known in the art. Thevarious implementations of the source code and object and byte codes canbe held on a computer-readable storage medium or embodied on atransmission medium in a carrier wave. The server system 16 includesthree primary software modules, database module 125, diagnostic module126, and feedback module 128, which perform integrated functions asfollows.

First, the database module 125 organizes the individual patient carerecords 23 stored in the database 17 (shown in FIG. 1) and efficientlystores and accesses the reference baseline 26, monitoring sets 27, andpatient care data maintained in those records. Any type of databaseorganization could be utilized, including a flat file system,hierarchical database, relational database, or distributed database,such as provided by database vendors, such as Oracle Corporation,Redwood Shores, Calif.

Next, the diagnostic module 126 makes findings of atrial fibrillationand attendant cardiovascular consequences through the implantablemedical device 12 and, in a more limited fashion, the external medicaldevice 26, and categorizes the findings into reduced exercise capacity-,respiratory distress-, palpitations-, and syncope/near syncope-relatedatrial fibrillation based on the comparison and analysis of the datameasures from the reference baseline 26 and monitoring sets 27. Thediagnostic module includes three modules: comparison module 130,analysis module 131, and quality of life module 132. The comparisonmodule 130 compares recorded and derived measures retrieved from thereference baseline 26, if used, and monitoring sets 27 to indicatorthresholds 129. The database 17 stores individual patient care records23 for patients suffering from various health disorders and diseases forwhich they are receiving remote patient care. For purposes of comparisonand analysis by the comparison module 130, these records can becategorized into peer groups containing the records for those patientssuffering from similar disorders, as well as being viewed in referenceto the overall patient population. The definition of the peer group canbe progressively refined as the overall patient population grows. Toillustrate, FIG. 6 is a record view showing, by way of example, a set ofpartial patient care records for care of patients with atrialfibrillation stored in the database 17 for three patients, Patient 1,Patient 2, and Patient 3. For each patient, three sets of peer measures,X, Y, and Z. are shown. Each of the measures, X, Y, and Z, could beeither collected or derived measures from the reference baseline 26, ifused, and monitoring sets 27.

The same measures are organized into time-based sets with Set 0representing sibling measures made at a reference time t=0. Similarly,Set n−2, Set n−1 and Set n each represent sibling measures made at laterreference times t=n−2, t=n−1 and t=n, respectively. Thus, for a givenpatient, such as Patient 1, serial peer measures, such as peer measureX₀ through X_(n), represent the same type of patient informationmonitored over time. The combined peer measures for all patients can becategorized into a health disorder- or disease-matched peer group. Thedefinition of disease-matched peer group is a progressive definition,refined over time as the number of monitored patients grows. Measuresrepresenting different types of patient information, such as measuresX₀, Y₀, and Z₀, are sibling measures. These are measures which are alsomeasured over time, but which might have medically significant meaningwhen compared to each other within a set for an individual patient.

The comparison module 130 performs two basic forms of comparison. First,individual measures for a given patient can be compared to otherindividual measures for that same patient (self-referencing). Thesecomparisons might be peer-to-peer measures, that is, measures relatingto a one specific type of patient information, projected over time, forinstance, X_(n), X_(n−1), X_(n−2), . . . X₀, or sibling-to-siblingmeasures, that is, measures relating to multiple types of patientinformation measured during the same time period, for a single snapshot,for instance, X_(n), Y_(n), and Z_(n), or projected over time, forinstance, X_(n), Y_(n), Z_(n), X_(n−1), Y_(n−1), Z_(n−1), X_(n−2),Y_(n−2), Z_(n−2), . . . X₀, Y₀, Z₀. Second, individual measures for agiven patient can be compared to other individual measures for a groupof other patients sharing the same disorder- or disease-specificcharacteristics (peer group referencing) or to the patient population ingeneral (population referencing). Again, these comparisons might bepeer-to-peer measures projected over time, for instance, X_(n), X_(n′),X_(n″), X_(n−1), X_(n−1′), X_(n−1″), X_(n−2), X_(n−2′), X_(n−2″) . . .X₀, X_(0′), X_(0″), or comparing the individual patient's measures to anaverage from the group. Similarly, these comparisons might besibling-to-sibling measures for single snapshots, for instance, X_(n),X_(n′), X_(n″), Y_(n), Y_(n′), Y_(n″), and Z_(n), Z_(n′), Z_(n″), orprojected over time, for instance, X_(n), X_(n′), X_(n″), Y_(n), Y_(n′),Y_(n″), Z_(n), Z_(n′), Z_(n″), X_(n−1), X_(n−1′), X_(n−1″), Y_(n−1),Y_(n−1′), Y_(n−1″), Z_(n−1), Z_(n−1′), Z_(n−1″), X_(n−2), X_(n−2′),X_(n−2″), Y_(n−2), Y_(n−2′), Y_(n−2″), Z_(n−2), Z_(n−2′), Z_(n−2″) . . .X₀, X_(0′), X_(0″), Y₀, Y_(0′), Y_(0″), and Z₀, Z_(0′), Z_(0″). Otherforms of comparisons are feasible, including multiple disease diagnosesfor diseases exhibiting similar abnormalities in physiological measuresthat might result from a second disease but manifest in differentcombinations or onset in different temporal sequences.

FIG. 7 is a Venn diagram showing, by way of example, peer group overlapbetween the partial patient care records 23 of FIG. 1. Each patient carerecord 23 includes characteristics data 350, 351, 352, includingpersonal traits, demographics, medical history, and related personaldata, for patients 1, 2 and 3, respectively. For example, thecharacteristics data 350 for patient 1 might include personal traitswhich include gender and age, such as male and an age between 40-45; ademographic of resident of New York City; and a medical historyconsisting of anterior myocardial infraction, paroxysmal atrialfibrillation and diabetes. Similarly, the characteristics data 351 forpatient 2 might include identical personal traits, thereby resulting inpartial overlap 353 of characteristics data 350 and 351. Similarcharacteristics overlap 354, 355, 356 can exist between each respectivepatient. The overall patient population 357 would include the universeof all characteristics data. As the monitoring population grows, thenumber of patients with personal traits matching those of the monitoredpatient will grow, increasing the value of peer group referencing. Largepeer groups, well matched across all monitored measures, will result ina well known natural history of disease and will allow for more accurateprediction of the clinical course of the patient being monitored. If thepopulation of patients is relatively small, only some traits 356 will beuniformly present in any particular peer group. Eventually, peer groups,for instance, composed of 100 or more patients each, would evolve underconditions in which there would be complete overlap of substantially allsalient data, thereby forming a powerfill core reference group for anynew patient being monitored.

Referring back to FIG. 5, the analysis module 131 analyzes the resultsfrom the comparison module 130, which are stored as a combined measuresset 95 (not shown), to a set of indicator thresholds 129, as furtherdescribed below with reference to FIGS. 8A-8B. Similarly, the quality oflife module 132 compares quality of life and symptom measures set 25 a,25 b from the reference baseline 26 and monitoring sets 27, the resultsof which are incorporated into the comparisons performed by the analysismodule 131, in part, to either refute or support the findings based onphysiological “hard” data. Finally, the feedback module 128 providesautomated feedback to the individual patient based, in part, on thepatient status indicator 127 generated by the diagnostic module 126. Asdescribed above, the feedback could be by electronic mail or byautomated voice mail or facsimile. The feedback can also includenormalized voice feedback, such as described in the related,commonly-owned U.S. patent application, Ser. No. 09/361,777, pending,filed Jul. 26, 1999, the disclosure of which is incorporated herein byreference. In addition, the feedback module 128 determines whether anychanges to interventive measures are appropriate based on thresholdstickiness (“hysteresis”) 133, as further described below with referenceto FIG. 16. The threshold stickiness 133 can prevent fickleness indiagnostic routines resulting from transient, non-trending andnon-significant fluctuations in the various collected and derivedmeasures in favor of more certainty in diagnosis. In a furtherembodiment of the present invention, the feedback module 128 includes apatient query engine 134 which enables the individual patient 11 tointeractively query the server system 16 regarding the diagnosis,therapeutic maneuvers, and treatment regimen. Conversely, the patientquery engines 134, found in interactive expert systems for diagnosingmedical conditions, can interactively query the patient. Using thepersonal computer 18 (shown in FIG. 1), the patient can have aninteractive dialogue with the automated server system 16, as well ashuman experts as necessary, to self assess his or her medical condition.Such expert systems are well known in the art, an example of which isthe MYCIN expert system developed at Stanford University and describedin Buchanan, B. & Shortlife, E., “RULE-BASED EXPERT SYSTEMS. The MYCINExperiments of the Stanford Heuristic Programming Project,”Addison-Wesley (1984). The various forms of feedback described abovehelp to increase the accuracy and specificity of the reporting of thequality of life and symptomatic measures.

FIGS. 8A-8B are flow diagrams showing a method for diagnosing andmonitoring the outcomes of atrial fibrillation 135 using an automatedcollection and analysis patient care system 10 in accordance with thepresent invention. First, the indicator thresholds 129 (shown in FIG. 5)are set (block 136) by defining a quantifiable physiological measure ofa pathophysiology resulting from atrial fibrillation and relating toeach type of patient information in the combined device and derivedmeasures set 95 (shown in FIG. 4). The actual values of each indicatorthreshold can be finite cutoff values, weighted values, or statisticalranges, as discussed below with reference to FIGS. 11A-11D. Next, thereference baseline 26 (block 137) and monitoring sets 27 (block 138) areretrieved from the database 17, as further described below withreference to FIGS. 9 and 10, respectively. Each measure in the combineddevice and derived measures set 95 is tested against the thresholdlimits defined for each indicator threshold 129 (block 139), as furtherdescribed below with reference to FIGS. 11A-11D. The potential onset,progression (where progression of atrial fibrillation is defined as aventricular rate increase and/or a deterioration in physiologicalcardiovascular and cardiopulmonary measures regardless of rate change),regression (where regression of atrial fibrillation is defined as itsoffset, a decrease in ventricular rate, and/or an improvement incardiovascular and cardiopulmonary physiological measures), or statusquo of atrial fibrillation is then evaluated (block 140) based upon thefindings of the threshold limits tests (block 139), as further describedbelow with reference to FIGS. 13A-13B, 14A-14B, 15A-15B.

In a further embodiment, multiple near-simultaneous disorders areconsidered in addition to primary atrial fibrillation. Primaryatrialfibrillation is defined as the onset or progression of atrialfibrillation without obvious inciting identifiable cause. Secondaryatrialfibrillation is defined as the onset or progression of atrialfibrillation (in a patient with or without a history of previouslydocumented atrial fibrillation) from another disease process, such ascongestive heart failure, myocardial ischemia, coronary insufficiency,respiratory insufficiency, specific identifiable electrophysiologicalabnormalities, and so forth. Other health disorders and diseases canpotentially share the same forms of symptomatology as atrialfibrillation, such as myocardial ischemia, respiratory insufficiency,pneumonia, exacerbation of chronic bronchitis, renal failure,sleep-apnea, stroke, anemia, other cardiac arrhythmias, and so forth. Ifmore than one abnormality is present, the relative sequence andmagnitude of onset of abnormalities in the monitored measures becomesmost important in sorting and prioritizing disease diagnosis andtreatment.

Thus, if other disorders or diseases are being cross-referenced anddiagnosed (block 141), their status is determined (block 142). In thedescribed embodiment, the operations of ordering and prioritizingmultiple near-simultaneous disorders (box 151) by the testing ofthreshold limits and analysis in a manner similar to congestive heartfailure as described above, preferably in parallel to the presentdetermination, is described in the related, commonly-owned U.S. patentapplication, Ser. No. 09/441,405, entitled “Automated Collection AndAnalysis Patient Care System And Method For Ordering And PrioritizingMultiple Health Disorders To Identify An Index Disorder,” pending, filedNov. 16, 1999, the disclosure of which is incorporated herein byreference. If atrial fibrillation is due to an obvious inciting cause,i.e., secondary atrial fibrillation, (block 143), an appropriatetreatment regimen is adopted that includes treatment of secondarydisorders, e.g., myocardial ischemia, respiratory insufficiency, and soforth (block 144), as well as atrial fibrillation if needed, and asuitable patient status indicator 127 for atrial fibrillation isprovided (block 146) to the patient indicating diagnosis and managementrecommendations for both atrial fibrillation and inciting causes.Suitable devices and approaches to diagnosing and treating congestiveheart failure, myocardial infarction, and respiratory insufficiency aredescribed in related, commonly-owned U.S. patent applications, Ser. No.09/441,623, entitled “Automated Collection And Analysis Patient CareSystem And Method For Diagnosing And Monitoring Congestive Heart FailureAnd Outcomes Thereof,” pending, filed Nov. 16, 1999; Ser. No.09/441,612, entitled “Automated Collection And Analysis Patient CareSystem And Method For Diagnosing And Monitoring Myocardial Ischemia AndOutcomes Thereof,” pending, filed Nov. 16, 1999; and Ser. No.09/442,125, entitled “Automated Collection And Analysis Patient CareSystem And Method For Diagnosing And Monitoring RespiratoryInsufficiency And Outcomes Thereof,” pending, filed Nov. 16, 1999, thedisclosures of which are incorporated herein by reference.

Otherwise, if primary atrial fibrillation is indicated (block 143), aprimary treatment regimen is followed (block 145). A patient statusindicator 127 for atrial fibrillation is provided (block 146) to thepatient regarding physical well-being, disease prognosis, including anydeterminations of disease onset, progression, regression, or status quo,and other pertinent medical and general information of potentialinterest to the patient.

Finally, in a further embodiment, if the patient submits a query to theserver system 16 (block 147), the patient query is interactivelyprocessed by the patient query engine (block 148). Similarly, if theserver elects to query the patient (block 149), the server query isinteractively processed by the server query engine (block 150). Themethod then terminates if no further patient or server queries aresubmitted.

FIG. 9 is a flow diagram showing the routine for retrieving referencebaseline sets 137 for use in the method of FIGS. 8A-8B. The purpose ofthis routine is to retrieve the appropriate reference baseline sets 26,if used, from the database 17 based on the types of comparisons beingperformed. First, if the comparisons are self referencing with respectto the measures stored in the individual patient care record 23 (block152), the reference device and derived measures set 24 a and referencequality of life and symptom measures set 25 a, if used, are retrievedfor the individual patient from the database 17 (block 153). Next, ifthe comparisons are peer group referencing with respect to measuresstored in the patient care records 23 for a health disorder- ordisease-specific peer group (block 154), the reference device andderived measures set 24 a and reference quality of life and symptommeasures set 25 a, if used, are retrieved from each patient care record23 for the peer group from the database 17 (block 155). Data for eachmeasure (e.g., minimum, maximum, averaged, standard deviation (SD), andtrending data) from the reference baseline 26 for the peer group is thencalculated (block 156). Finally, if the comparisons are populationreferencing with respect to measures stored in the patient care records23 for the overall patient population (block 157), the reference deviceand derived measures set 24 a and reference quality of life and symptommeasures set 25 a, if used, are retrieved from each patient care record23 from the database 17 (block 158). Minimum, maximum, averaged,standard deviation, and trending data and other numerical processesusing the data, as is known in the art, for each measure from thereference baseline 26 for the peer group is then calculated (block 159).The routine then returns.

FIG. 10 is a flow diagram showing the routine for retrieving monitoringsets 138 for use in the method of FIGS. 8A-8B. The purpose of thisroutine is to retrieve the appropriate monitoring sets 27 from thedatabase 17 based on the types of comparisons being performed. First, ifthe comparisons are self referencing with respect to the measures storedin the individual patient care record 23 (block 160), the device andderived measures set 24 b and quality of life and symptom measures set25 b, if used, are retrieved for the individual patient from thedatabase 17 (block 161). Next, if the comparisons are peer groupreferencing with respect to measures stored in the patient care records23 for a health disorder- or disease-specific peer group (block 162),the device and derived measures set 24 b and quality of life and symptommeasures set 25 b, if used, are retrieved from each patient care record23 for the peer group from the database 17 (block 163). Data for eachmeasure (e.g., minimum, maximum, averaged, standard deviation, andtrending data) from the monitoring sets 27 for the peer group is thencalculated (block 164). Finally, if the comparisons are populationreferencing with respect to measures stored in the patient care records23 for the overall patient population (block 165), the device andderived measures set 24 b and quality of life and symptom measures set25 b, if used, are retrieved from each patient care record 23 from thedatabase 17 (block 166). Minimum, maximum, averaged, standard deviation,and trending data and other numerical processes using the data, as isknown in the art, for each measure from the monitoring sets 27 for thepeer group is then calculated (block 167). The routine then returns.

FIGS. 11A-11D are flow diagrams showing the routine for testingthreshold limits 139 for use in the method of FIG. 8A and 8B. Thepurpose of this routine is to analyze, compare, and log any differencesbetween the observed, objective measures stored in the referencebaseline 26, if used, and the monitoring sets 27 to the indicatorthresholds 129. Briefly, the routine consists of tests pertaining toeach of the indicators relevant to diagnosing and monitoring theoutcomes of atrial fibrillation and cardiovascular consequences. Thethreshold tests focus primarily on: (1) changes to and rates of changefor the indicators themselves, as stored in the combined device andderived measures set 95 (shown in FIG. 4) or similar data structure; and(2) violations of absolute threshold limits which trigger an alert. Thetiming and degree of change may vary with each measure and with thenatural fluctuations noted in that measure during the reference baselineperiod. In addition, the timing and degree of change might also varywith the individual and the natural history of a measure for thatpatient.

One suitable approach to performing the threshold tests uses a standardstatistical linear regression technique using a least squares error fit.The least squares error fit can be calculated as follows:$\begin{matrix}{y = {\beta_{0} + {\beta_{1}x}}} & (1) \\{\beta = \frac{{SS}_{xy}}{{SS}_{xx}}} & (2) \\{{SS}_{xy} = {{\sum\limits_{i = 1}^{n}\quad {x_{i}y_{i}}} - \frac{\left( {\sum\limits_{i = 1}^{n}\quad x_{i}} \right)\left( {\sum\limits_{i = 1}^{n}\quad y_{i}} \right)}{n}}} & (3) \\{{SS}_{xx} = {{\sum\limits_{i = 1}^{n}\quad x_{i}^{2}} - \frac{\left( {\sum\limits_{i = 1}^{n}\quad x_{i}} \right)^{2}}{n}}} & (4)\end{matrix}$

where n is the total number of measures, x_(i) is the time of day formeasure i, and y_(i) is the value of measure i, β₁ is the slope, and β₀is the y-intercept of the least squares error line. A positive slope ⊕₁indicates an increasing trend, a negative slope β₁ indicates adecreasing trend, and no slope indicates no change in patient conditionfor that particular measure. A predicted measure value can be calculatedand compared to the appropriate indicator threshold 129 for determiningwhether the particular measure has either exceeded an acceptablethreshold rate of change or the absolute threshold limit.

For any given patient, three basic types of comparisons betweenindividual measures stored in the monitoring sets 27 are possible: selfreferencing, peer group, and general population, as explained above withreference to FIG. 6. In addition, each of these comparisons can includecomparisons to individual measures stored in the pertinent referencebaselines 24.

The indicator thresholds 129 for detecting a trend indicating an adverseconsequence of atrial fibrillation or a state of imminent or likelycardiovascular or cardiopulmonary deterioration, for example, over a oneweek time period, can be as follows:

(1) Heart rate (block 170): If the ventricular heart rate during atrialfibrillation has increased over 1.0 SD from the mean heart rate in thereference baseline 26, if used (block 171), the increased ventricularheart rate and time span over which it occurs are logged in the combinedmeasures set 95 (block 172).

(2) Respiratory rate (block 173): If the respiratory rate has increasedover 1.0 SD from the mean respiratory rate in the reference baseline 26,if used (block 174), the increased respiratory rate and time span overwhich it occurs are logged in the combined measures set 95 (block 175).

(3) Pulmonary artery diastolic pressure (PADP) (block 176) reflects leftventricular filling pressure and is a measure of left ventriculardysfunction. Ideally, the left ventricular end diastolic pressure(LVEDP) should be monitored, but in practice is difficult to measure.Consequently, without the LVEDP, the PADP, or derivatives thereof, issuitable for use as an alternative to LVEDP in the present invention. Ifthe PADP has increased over 1.0 SD from the mean PADP in the referencebaseline 26 (block 177), the increased PADP and time span over whichthat increase occurs, are logged in the combined measures set 95 (block178). Other cardiac pressures or derivatives could also apply.

(4) Transthoracic impedance (block 179): If the transthoracic impedancehas decreased over 1.0 SD from the mean transthoracic impedance in thereference baseline 26 (block 180), the decreased transthoracic impedanceand time span are logged in the combined measures set 95 (block 181).

(5) Arterial oxygen score (block 182): If the arterial oxygen score hasdecreased over 1.0 SD from the arterial oxygen score in the referencebaseline 26 (block 183), the decreased arterial oxygen score and timespan are logged in the combined measures set 95 (block 184).

(6) Venous oxygen score (block 185): If the venous oxygen score hasdecreased over 1.0 SD from the mean venous oxygen score in the referencebaseline 26 (block 186), the decreased venous oxygen score and time spanare logged in the combined measures set 95 (block 187).

(7) Cardiac output (block 188): If the cardiac output has decreased over1.0 SD from the mean cardiac output in the reference baseline 26 (block189), the decreased cardiac output and time span are logged in thecombined measures set 95 (block 190).

(8) Patient activity score (block 191): If the mean patient activityscore has decreased over 1.0 SD from the mean patient activity score inthe reference baseline 26 (block 192), the decreased patient activityscore and time span are logged in the combined measures set 95 (block193).

(9) Exercise tolerance quality of life (QOL) measures (block 194): Ifthe exercise tolerance QOL has decreased over 1.0 SD from the meanexercise tolerance in the reference baseline 26 (block 195), thedecrease in exercise tolerance and the time span over which it occursare logged in the combined measures set 95 (block 196).

(10) Respiratory distress quality of life (QOL) measures (block 197): Ifthe respiratory distress QOL measure has deteriorated by more than 1.0SD from the mean respiratory distress QOL measure in the referencebaseline 26 (block 198), the increase in respiratory distress and thetime span over which it occurs are logged in the combined measures set95 (block 199).

(11) Atrial fibrillation (block 200): The presence or absence of atrialfibrillation (AF) is determined and, if present (block 201), atrialfibrillation is logged (block 202).

(12) Rhythm changes (block 203): The type and sequence of rhythm changesis significant and is determined based on the timing of the relevantrhythm measure, such as sinus rhythm. For instance, a finding that arhythm change to atrial fibrillation precipitated circulatory measureschanges can indicate therapy directions against atrial fibrillationrather than primary progression of atrial fibrillation. Thus, if thereare rhythm changes (block 204), the sequence of the rhythm changes andtime span are logged (block 205).

Note also that an inversion of the indicator thresholds 129 definedabove could similarly be used for detecting a trend in diseaseregression. One skilled in the art would recognize that these measureswould vary based on whether or not they were recorded during rest orduring activity and that the measured activity score can be used toindicate the degree of patient rest or activity. The patient activityscore can be determined via an implantable motion detector, for example,as described in U.S. Pat. No. 4,428,378, issued Jan. 31, 1984, toAnderson et al., the disclosure of which is incorporated herein byreference.

FIGS. 12A-12B are flow diagrams showing the routine for evaluating theonset, progression, regression and status quo of atrial fibrillation 140for use in the method of FIG. 8A and 8B. The purpose of this routine isto evaluate the presence of sufficient indicia to warrant a diagnosis ofthe onset, progression, regression, and status quo of atrialfibrillation and the consequential changes, if any, of comorbiddisorders. Quality of life and symptom measures set 25 can be includedin the evaluation (block 220) by determining whether any of theindividual quality of life and symptom measures set 25 have changedrelative to the previously collected quality of life and symptommeasures from the monitoring sets 27 and the reference baseline 26, ifused. For example, a deterioration in the shortness of breath measure 87and exercise tolerance measure 89 would corroborate a finding of atrialfibrillation exacerbating cardiovascular or cardiopulmonary measures.Similarly, a transition from NYHA Class II to NYHA Class III wouldindicate a deterioration or, conversely, a transition from NYHA ClassIII to NYHA Class II status would indicate improvement or progress.Incorporating the quality of life and symptom measures set 25 into theevaluation can help, in part, to refute or support findings based onphysiological data. Next, a determination as to whether any changes tointerventive measures are appropriate based on threshold stickiness(“hysteresis”) is made (block 221), as further described below withreference to FIG. 16.

The routine returns upon either the determination of a finding orelimination of all factors as follows. A diagnosis of atrialfibrillation is made (block 222) via one of many methods known in theart through the implantable medical device 12 and, in a more limitedfashion, via the external medical device 26, such as described in U.S.Pat. No. 5,931,857 ('857) to Prieve et al. and U.S. Pat. No. 5,855,593('593) to Olson et al, the disclosures of which are incorporated hereinby reference. If atrial fibrillation has occurred (block 223), thefindings are categorized into reduced exercise capacity-, respiratorydistress-palpitations-, and syncope-/near syncope-related atrialfibrillation as follows. First, if a finding of atrial fibrillation wasnot previously diagnosed (block 224), a determination categorizingdisease onset is made (block 225), as further described below withreference to FIGS. 13A-13B. Otherwise, if atrial fibrillation waspreviously diagnosed (block 224), a further determination categorizingeither disease progression (block 226) or regression (block 227) ismade, as further described below with reference to FIGS. 14A-14B and15A-15B, respectively. If, upon evaluation, neither disease onset (block225), progression (block 226) or regression (block 227) is indicated, afinding of status quo is appropriate (block 228) and duly noted (block229). Finally, if status quo does not exist, that is, atrialfibrillation has occurred, either as an initial onset, progression orregression (block 230), the occurrence is managed from the perspectiveof an effort to terminate atrial fibrillation and restore sinus rhythm,to decrease ventricular rate response, and/or to minimize theconsequences of the presence of atrial fibrillation, e.g., provideanticoagulants to prevent a stroke and/or diuretics to reverseprogression in congestive heart failure (block 230), as furtherdescribed below with reference to FIGS. 17A-17B. The routine thenreturns.

FIGS. 13A-13B are flow diagrams showing the routine for categorizing anonset of atrial fibrillation 225 for use in the routine of FIGS.12A-12B. An effort is made to categorize atrial fibrillation manifestingprimarily as resulting in reduced exercise capacity (block 243),increased respiratory distress (block 249), and/or palpitations (block251). The clinical aspects of atrial fibrillation are described, by wayof example, in E. Braunwald, ed., “Heart Disease—A Textbook ofCardiovascular Medicine,” Chs. 1 and 22, W.B. Saunders Co. (1997), thedisclosure of which is incorporated herein by reference.

In the described embodiment, the reduced exercise capacity, respiratorydistress, and palpitations findings (blocks 243, 249, 251) can beestablished by consolidating the individual indications (blocks 240-242,244-248, 250) in several ways. First, in a preferred embodiment, eachindividual indication (blocks 240-242, 244-248, 250) is assigned ascaled index value correlating with the relative severity of theindication. For example, decreased cardiac output (block 240) could bemeasured on a scale from ‘1’ to ‘5’ wherein a score of ‘1’ indicates nochange in cardiac output from the reference point, a score of ‘2’indicates a change exceeding 0.5 SD, a score of ‘3’ indicates a changeexceeding 1.0 SD, a score of ‘4’ indicates a change exceeding 2.0 SD,and a score of ‘5’ indicates a change exceeding 3.0 SD. The index valuefor each of the individual indications (blocks 240-242, 244-248, 250)can then either be aggregated or averaged with a result exceeding theaggregate or average maximum indicating an appropriate atrialfibrillation finding.

Preferably, all scores are weighted depending upon the assignments madefrom the measures in the reference baseline 26. For instance, arterialpartial pressure of oxygen 102 could be weighted more importantly thanrespiratory rate 104 if the respiratory rate in the reference baseline26 is particularly high at the outset, making the detection of furtherdisease progression from increases in respiratory rate, less sensitive.In the described embodiment, cardiac output receives the most weight indetermining a reduced exercise capacity finding, pulmonary arterydiastolic pressure receives the most weight in determining a respiratorydistress or dyspnea finding, and a transition from normal sinus rhythmto atrial fibrillation receives the most weight in determining apalpitations finding.

Alternatively, a simple binary decision tree can be utilized whereineach of the individual indications (blocks 240-242, 244-248, 250) iseither present or is not present. Any of the individual indications(blocks 240-242, 244-248, 250) should be present for the relevant effectof atrial fibrillation on cardiovascular and cardiopulmonary measures tobe affirmed as long as the atrial fibrillation is temporally related toonset.

Other forms of consolidating the individual indications (blocks 240-242,244-248, 250) are feasible.

FIGS. 14A-14B are flow diagrams showing the routine for categorizing aprogression or worsening of atrial fibrillation 226 for use in theroutine of FIGS. 12A-12B. The primary difference between thedeterminations of disease onset, as described with reference to FIGS.13A-13B, and disease progression is a demonstration of an increasedventricular rate response in atrial fibrillation or deterioration incardiovascular or cardiopulmonary measures regardless of ventricularrate during atrial fibrillation. Whereas, to define atrial fibrillationonset, the heart rhythm must transition from normal sinus rhythm (or anynon-atrial fibrillation rhythm) to atrial fibrillation as detected byany of the methods known in the art for heart rhythm diagnosis. Thus, arevised atrial fibrillation finding is possible based on the same threegeneral symptom categories: reduced exercise capacity (block 273),respiratory distress (block 279), and palpitations (block 281). The samefactors which need be indicated to warrant a diagnosis of atrialfibrillation onset and its consequences are also evaluated to determinedisease progression.

Similarly, FIGS. 15A-15B are flow diagrams showing the routine forcategorizing a regression or improving of atrial fibrillation 227 andits cardiovascular and cardiopulmonary consequences for use in theroutine of FIGS. 12A-12B. The same factors as described above withreference to FIGS. 13A-13B and 14A-14B, trending in opposite directionsfrom disease onset or progression, are evaluated to determine diseaseregression. As primary cardiac disease considerations, multipleindividual indications (blocks 300-302, 304-308, 310) should be presentfor the three principal findings of atrial fibrillation related reducedexercise capacity (block 303), atrial fibrillation related respiratorydistress (block 309), and palpitations (block 311), to indicate diseaseregression.

FIG. 16 is a flow diagram showing the routine for determining thresholdstickiness (“hysteresis”) 221 for use in the method of FIGS. 12A-12B.Stickiness, also known as hysteresis, is a medical practice doctrinewhereby a diagnosis or therapy will not be changed based upon small ortemporary changes in a patient reading, even though those changes mighttemporarily move into a new zone of concern. For example, if a patientmeasure can vary along a scale of ‘1’ to ‘10’ with ‘10’ being worse, atransient reading of ‘6’ standing alone, on a patient who hasconsistently indicated a reading of ‘5’ for weeks will not warrant achange in diagnosis without a definitive prolonged deterioration firstbeing indicated. Stickiness dictates that small or temporary changes incardiovascular or cardiopulmonary physiology associated with atrialfibrillation onset, progression or regression require more diagnosticcertainty, as confirmed by the persistence of the changes, than largechanges would require for any of the monitored (device) measures.Stickiness also makes reversal of important diagnostic decisions,particularly those regarding life-threatening disorders, more difficultthan reversal of diagnoses of modest import. As an example, automaticexternal defibrillators (AEDs) manufactured by Heartstream, a subsidiaryof Agilent Technologies, Seattle, Wash., monitor heart rhythms andprovide interventive shock treatment for the diagnosis of ventricularfibrillation. Once diagnosis of ventricular fibrillation and a decisionto shock the patient has been made, a pattern of no ventricularfibrillation must be indicated for a relatively prolonged period beforethe AED changes to a “no-shock” decision. As implemented in this AEDexample, stickiness mandates certainty before a decision to shock isdisregarded.

In practice, stickiness also dictates that acute deteriorations indisease state are treated aggressively while chronic, more slowlyprogressing disease states are treated in a more tempered fashion. Thus,if the patient status indicates a status quo (block 330), no changes intreatment or diagnosis are indicated and the routine returns. Otherwise,if the patient status indicates a change away from status quo (block330), the relative quantum of change and the length of time over whichthe change has occurred is determinative. If the change of approximately0.5 SD has occurred over the course of about one month (block 331), agradually deteriorating condition exists (block 332) and a very tempereddiagnostic, and if appropriate, treatment program is undertaken. If thechange of approximately 1.0 SD has occurred over the course of about oneweek (block 333), a more rapidly deteriorating condition exists (block334) and a slightly more aggressive diagnostic, and if appropriate,treatment program is undertaken. If the change of approximately 2.0 SDhas occurred over the course of about one day (block 335), an urgentlydeteriorating condition exists (block 336) and a moderately aggressivediagnostic, and if appropriate, treatment program is undertaken. If thechange of approximately 3.0 SD has occurred over the course of about onehour (block 337), an emergency condition exists (block 338) and animmediate diagnostic, and if appropriate, treatment program isundertaken as is practical. Finally, if the change and duration falloutside the aforementioned ranges (blocks 331-338), an exceptionalcondition exists (block 339) and the changes are reviewed manually, ifnecessary. The routine then returns. These threshold limits and timeranges may then be adapted depending upon patient history and peer-groupguidelines.

The form of the revised treatment program depends on the extent to whichthe time span between changes in the device measures exceed thethreshold stickiness 133 (shown in FIG. 5) relating to that particulartype of device measure. For example, threshold stickiness 133 indicatorfor monitoring a change in heart rate in a chronic patient sufferingfrom atrial fibrillation might be 10% over a week. Consequently, achange in average heart rate 96 (shown in FIG. 4) from 80 bpm to 95 bpmover a seven day period, where a 14 beat per minute average change wouldequate to a 1.0 SD change, would exceed the threshold stickiness 133 andwould warrant a revised medical diagnosis perhaps of diseaseprogression. One skilled in the art would recognize the indications ofacute versus chronic disorders which will vary upon the type of disease,patient health status, disease indicators, length of illness, and timingof previously undertaken interventive measures, plus other factors.

FIGS. 17A-17B is a flow diagram showing the routine for managing theconsequences of atrial fibrillation 230 for use in the routine of FIGS.12A-12B. The management of atrial fibrillation focuses principally onrestoring normal sinus rhythm and controlling ventricular rate response(VRR). However, effective atrial fibrillation management requiresconsidering four individual areas of concern:cardiovascular/cardiopulmonary compromise, ventricular rate response,anticoagulation status, and associated symptoms, like the presence ofpalpitations. An overriding theme is that restoration of normal sinusrhythm should not be attempted for atrial fibrillation greater than orequal to 48 hours in duration in the absence of anticoagulation orserious cardiovascular/cardiopulmonary compromise to prevent stroke.Consequently, therapy should usually be directed to control ofventricular rate response under such circumstances.

Each of these areas of concern may potentially overlap and requirecoordinated therapeutic treatment. The management process that follows,although outlined in linear, sequential fashion, can be performed in asimultaneous manner, where clinically reasonable and necessary. Oneconcern of persistent atrial fibrillation is a time-based threat ofthromboembolic disease if atrial fibrillation persists for longer than48 hours and the patient's blood is not anticoagulated. Atrialfibrillation should, if possible and clinically reasonable, beterminated if atrial fibrillation reaches a duration exceeding 48 hours.In addition, atrial fibrillation of any duration may be accompanied bycardiovascular decompensation, including a decrease in cardiac output,an increase in cardiac filling pressures, a decrease in blood pressure,a decrease in oxygenation, and an increase in myocardial ischemia,particularly if atrial fibrillation presents in conjunction withcomorbid disorders. Again, if possible and clinically reasonable, atrialfibrillation should be terminated. Although atrial fibrillation may, inand of itself, affect cardiovascular physiology adversely, a componentof the response may be due to a ventricular rate response which iseither too rapid or too slow. Thus, control of ventricular rate responseconstitutes a third management concern. Palpitations are caused by anirregular heartbeat which, while possibly uncomfortable to a patient,usually need only be monitored and not treated. In the event ofdisabling palpitations, or other related symptoms such as dyspnea orfatigue, however, atrial fibrillation can be electrically orpharmacologically terminated.

The four areas of concern regarding atrial fibrillation management areaddressed as follows. First, if a cardiovascular/cardiopulmonarycompromise exists (block 400), the compromise must be actively managed(block 401), as further described below with reference to FIGS. 18A-18D.After the completion of cardiovascular/cardiopulmonary compromisemanagement (block 401), if normal sinus rhythm has been restored (block402), the routine returns. If ventricular rate response isinappropriate, that is, either too rapid or too slow (block 403),ventricular rate response must be actively managed (block 404), asfurther described below with reference to FIG. 19. After the completionof ventricular rate response management (block 404), if ventricular rateresponse has been controlled (block 405), the routine returns. Ifanticoagulation management is required (block 406), such management isundertaken (block 407), as further described below with reference toFIG. 20. After the completion of anticoagulation management (block 407),if normal sinus rhythm has been restored (block 408), the routinereturns. Otherwise, if palpitations/symptoms are present (block 409),the palpitations/symptoms are actively managed (block 410), as furtherdescribed below with reference to FIG. 21. After the completion ofpalpitations/symptoms management (block 410), if normal sinus rhythm hasbeen restored (block 411), the routine returns. Finally, if none ofcardiovascular/cardiopulmonary compromise (block 400), inappropriateventricular rate response (block 403), anticoagulation management (block406), or palpitations/symptoms (block 409) are presented, no furtheraction is taken and the routine returns.

FIGS. 18A-18D are flow diagrams showing the routine for managing acardiovascular/cardiopulmonary compromise 401 for use in the method ofFIGS. 17A-17B. The purpose of this routine is to determine anappropriate treatment regimen for a cardiovascular/cardiopulmonarycompromise by classifying the relative magnitude of change inphysiological measures obtained or derived from the device and derivedmeasures sets 24 a, 24 b (shown in FIG. 1) into ranges of severity. Thedegree of medical intervention varies proportionate to the severity,magnitude of change and the time span over which the change occurred.Thus, deterioration greater than or equal to 3.0 SD (block 430) requiresimmediate, aggressive therapy regardless of anticoagulation status,whereas deterioration greater than or equal to than 0.5 SD but less than1.0 SD (block 433) may require only modest therapy. Beginning withmaximum change, if the deterioration in physiological measures isgreater than or equal to 3.0 SD (block 430), aggressive atrialfibrillation therapy, as defined below, is undertaken (block 434).Otherwise, if the deterioration in physiological measures is greaterthan or equal to 2.0 SD but less than 3.0 SD (block 431), the durationof atrial fibrillation and usage of anticoagulation drug therapy isconsidered. Thus, if atrial fibrillation has lasted fewer than 48 hours(block 435) or if at least 48 hours or longer and with anticoagulationtherapy (block 437), aggressive atrial fibrillation therapy isundertaken (blocks 436, 438, respectively). Otherwise, if atrialfibrillation has lasted at least 48 hours or longer (block 435) butwithout anticoagulation therapy (block 437), anticoagulation managementis undertaken (block 439), as further described below with reference toFIG. 20.

Upon completion of anticoagulation management (block 435), a ventricularrate response analysis (blocks 440-444) is performed as follows. First,if ventricular rate response is acceptable (block 440), aggressiveatrial fibrillation therapy is undertaken (block 441). Otherwise, ifventricular rate response in not acceptable (block 440) and control ofventricular rate response is possible (block 442), ventricular rateresponse management is undertaken (block 443), as further describedbelow with reference to FIG. 19. Conversely, if ventricular rateresponse is not acceptable (block 442), control of ventricular rateresponse is not possible (block 442), and cardiovascular/cardiopulmonaryphysiology is deteriorating (block 444), aggressive atrial fibrillationtherapy is undertaken (block 445).

On the lower range of change in physiological measures, if thedeterioration in physiological measures is greater than 1.0 SD but lessthan 2.0 SD (block 432), the duration of atrial fibrillation and usageof anticoagulation drug therapy is considered. Thus, if atrialfibrillation has lasted fewer than 48 hours (block 446), moderate atrialfibrillation therapy, as defined below, is undertaken (block 447). Ifnormal sinus rhythm has been restored (block 448), no further action isrequired. Otherwise, ventricular rate response management is undertaken(block 449), as further described below with reference to FIG. 19. Ifatrial fibrillation has lasted at least 48 hours or longer (block 446),the administration of anticoagulation drug therapy is considered. Ifanticoagulation drug therapy has already been undertaken (block 450),moderate atrial fibrillation therapy is undertaken (block 451).Otherwise, anticoagulation management is undertaken (block 452), asfurther described below with reference to FIG. 20.

Upon completion of anticoagulation management (block 452), a ventricularrate response analysis (blocks 453-458) is performed during atrialfibrillation as follows. First, if ventricular rate response isacceptable (block 453), cardiovascular/cardiopulmonary compromise ismonitored (block 454). If the cardiovascular/cardiopulmonary statusshows deterioration (block 455), the anticoagulation status is monitored(block 456) and, if fewer than three weeks have elapsed (block 457),therapy is dictated by cardiovascular/cardiopulmonary status (block454). Otherwise, if appropriate anticoagulation drug therapy hascontinued for at least three weeks with no substantial change incardiovascular/cardiopulmonary compromise status (block 455), the fullrange of atrial fibrillation therapies are slowly and incrementallyapplied, that is, from modest to moderate to aggressive, as isreasonably necessary and matched to the patient's condition (block 458).

Finally, if the deterioration in physiological measures at the onset ofatrial fibrillation is greater than 0.5 SD but less than 1.0 SD (block433), the duration of atrial fibrillation and usage of anticoagulationdrug therapy is again considered. Thus, if atrial fibrillation haslasted fewer than 48 hours (block 459), modest atrial fibrillationtherapy, as defined below, is undertaken (block 460). However, if atrialfibrillation has lasted at least 48 hours or longer (block 459), theadministration of anticoagulation drug therapy is considered. Ifanticoagulation drug therapy has already been undertaken (block 461),modest atrial fibrillation therapy is undertaken (block 462). Otherwise,anticoagulation management is undertaken (block 463), as furtherdescribed below with reference to FIG. 20.

Upon completion of anticoagulation management (block 463), a ventricularrate response analysis (blocks 464-470) is performed as follows. First,if ventricular rate response is acceptable (block 464), no furtheraction is taken. Otherwise, cardiovascular/cardiopulmonary compromise ismonitored (block 466) using a standard cardiovascular/cardiopulmonarymonitoring procedure (box 465). If the cardiovascular/cardiopulmonarystatus shows a worsening of the atrial fibrillation condition (block467), the compromise is managed (block 468) by recursively performingthe present routine. Otherwise, if the condition is improving (ormaintaining status quo) (block 467) and the anticoagulation drug therapystatus is acceptable (block 469), the full range of atrial fibrillationtherapies are slowly and incrementally applied, that is, from modest tomoderate to aggressive, as is reasonably necessary and matched to thepatient's condition (block 470). The routine then returns.

Note if the deterioration in physiological measures is less than 0.5 SD(block 433), no action is taken unless dictated bycardiovascular/cardiopulmonary measures.

FIG. 19 is a flow diagram showing the routine for managing ventricularrate response 404 for use in the method of FIGS. 17A-17B. The purpose ofthis routine is to bring ventricular rate response into a 50-90 beatsper minute (bpm) average range. Thus, if the average ventricular rateresponse is within a “good” range of 50-90 bpm (block 480), no furtheraction need be taken and the routine returns. Otherwise, if the averageventricular rate response is not less than 50 bpm, that is, in excess of90 bpm and thence too fast (block 481), actions to decrease theventricular pacing rate are considered. First, electrical therapy isundertaken (block 483) if such therapy is possible (block 482), such asdescribed in U.S. Pat. No. 5,356,425 to Bardy et al., the disclosure ofwhich is incorporated herein by reference. If the electrical therapy wasnot effective (block 484) or if electrical therapy is not possible(block 482), drug therapy to decrease atrioventricular (AV) nodeconduction is undertaken (block 485). If the drug therapy was noteffective (block 486), cardiovascular/cardiopulmonary compromise ismonitored (block 487) by performing the standard monitoring procedure(starting at block 471 in box 465 in FIGS. 18A-18D) where furthermanagement is dictated by the cardiovascular/cardiopulmonary measures.

If the average ventricular rate response is less than 50 bpm, that is,too slow (block 481), actions to increase the ventricular pacing rateare considered. If an increased ventricular pacing rate is possible(block 488), the ventricular pacing rate is increased, preferably towithin a range of 50-90 bpm (block 489), modified by the outcome incardiovascular/cardiopulmonary measures. Otherwise, if increasedventricular pacing is not possible (block 488) and antidromotropic drugs(drugs that slow atrioventricular node conduction) are present (block492), the antidromotropic drug therapy is decreased (block 492).Otherwise, if antidromotropic drugs are present (block 490),cardiovascular/cardiopulmonary compromise is monitored (block 491) byperforming the standard monitoring procedure (starting at block 471 inbox 465 in FIGS. 18A-18D). The routine then returns.

FIG. 20 is a flow diagram showing the routine for managinganticoagulation 407 for use in the method of FIGS. 17A-17B. The purposeof this routine is to initiate or adjust anticoagulation drug therapybased on the duration of atrial fibrillation and anticoagulation drugtherapy status. Anticoagulation drug therapy is not required if atrialfibrillation has persisted for less than 48 hours (block 520) or if thecondition of the patient contraindicates such therapy (block 521).Similarly, an adjustment to existing anticoagulation drug therapy isinappropriate if the anticoagulation is already adequate (block 522).Thus, if atrial fibrillation has lasted at least 48 hours or longer(block 520), anticoagulation is not contraindicated (block 521) and anypresent anticoagulation drug therapy is insufficient (block 522),anticoagulation drug therapy is started or adjusted, as appropriate(block 523) to maintain an International Normalized Ratio (INR) of2.0-3.0. The routine then returns.

FIG. 21 is a flow diagram showing the routine for managingpalpitations/symptoms 410 for use in the method of FIGS. 17A-17B. Thepurpose of this routine is to determine the proper quantum of atrialfibrillation therapy for a palpitating heartbeat, fatigue, dyspnea, orrelated symptoms. If palpitations/symptoms are present (block 540) anddisabling to the patient (block 541), moderate atrial fibrillationtherapy is undertaken (block 542). However, if the palpitations/symptomsare not disabling (block 541) and are merely irritating to the patient(block 543), modest atrial fibrillation is undertaken (block 544).Finally, if the palpitations/symptoms are not disabling (block 541) norirritating (block 543), no action is taken. The routine then returns.

A range of therapies with which to treat atrial fibrillation areavailable, including the following, non-exclusive exemplary list:

1. Electrical shock to restore normal sinus rhythm.

2. Antitachycardia pacing maneuvers to restore normal sinus rhythm.

3. Implantable medical device (or non-device) infusion of drugs torestore normal sinus rhythm.

4. Oral administration of drugs to restore normal sinus rhythm.

5. Electrical pacing maneuvers to decrease ventricular rate response.

6. Electrical pacing maneuvers to increase ventricular rate response.

7. Implantable medical device (or non-device) infusion of drugs todecrease ventricular rate response.

8. Implantable medical device (or non-device) infusion of drugs toincrease ventricular rate response.

9. Oral administration of drugs to decrease ventricular rate response.

10. Oral administration of drugs to increase ventricular rate response.

11. Discontinuation or withdrawal of drug therapy to restore normalsinus rhythm.

12. Discontinuation or withdrawal of drug therapy to decreaseventricular rate response.

13. Discontinuation or withdrawal of drug therapy to increaseventricular rate response. Other therapies for restoration of normalsinus rhythm or to favorably alter ventricular rate response are alsofeasible, as is known in the art.

The foregoing therapies can be approximately categorized into threegroupings of treatments to attempt to restore normal sinus rhythm or, asappropriate, to increase or decrease ventricular rate response, asfollows:

1. Aggressive Therapy (in order of preference):

a. Apply immediate electrical shock therapy to effect termination ofatrial fibrillation.

b. If electrical shock therapy is ineffective, administer most effectivedrug intravenously, regardless of drug side effects.

c. If drug thereby in isolation is ineffective, apply further electricalshock therapy in the presence of drug therapy.

2. Moderate Therapy (in order of preference):

a. Apply time restricted electrical pacing therapies, not more than onehour in duration.

b. If time restricted electrical pacing therapies are ineffective,administer most effective drug intravenously or by implantable medicaldevice (or non-device), regardless of drug side effects.

c. If time restricted electrical pacing and drug therapies areineffective, apply electrical shock therapy.

d. Administer oral drug therapy using agents of any potency and sideeffect profile.

e. Combine oral drug therapy with electrical therapy.

3. Modest Therapy (in order of preference):

a. Liberally apply electrical pacing therapies, not more than one day induration.

b. Administer oral drug therapy using agents with only modest sideeffects.

c. Only with patient approval, consider electrical shock or moreaggressive drug therapies.

The present invention provides several benefits. One benefit is improvedpredictive accuracy from the outset of patient care when a referencebaseline is incorporated into the automated diagnosis and whenphysiological measures immediately antecedent to the onset of atrialfibrillation can be examined to gauge the likelihood of precipitatingfactors, like heart failure, myocardial ischemia and pulmonaryinsufficiency as well as more subtle measures of cardiacelectrophysiology. This post-hoc analysis following each episode ofatrial fibrillation onset is likely to prove particular important inpatients with primary atrial fibrillation, that is those with no knownassociated diseases or explanations for the onset of atrialfibrillation.

A further benefit is an expanded knowledge base created by expanding themethodologies applied to a single patient to include patient peer groupsand the overall patient population. Collaterally, the informationmaintained in the database could also be utilized for the development offurther predictive techniques and for medical research purposes. Yet afurther benefit is the ability to hone and improve the predictivetechniques employed through a continual reassessment of patientoutcomes.

Other benefits include an automated, expert system approach to thecross-referral, consideration, and potential finding or elimination ofother diseases and health disorders with similar or related etiologicalindicators and for those other disorders that may have an impact onatrial fibrillation. Although disease specific markers will prove veryuseful in discriminating the underlying cause of symptoms, manydiseases, other than atrial fibrillation, will alter some of the samephysiological measures resulting from atrial fibrillation. Consequently,an important aspect of considering the potential impact of otherdisorders will be, not only the monitoring of atrial fibrillation onsetand offset and the ventricular rate during atrial fibrillation, but thesequencing of change and the temporal evolution of physiologicalmeasures, for example respiratory rate, arterial oxygenation, ST segmentevolution and cardiac output, to reflect the pathophysiologicalconsequences of atrial fibrillation onset, progression or regression inother disease processes.

Finally, the benefit of this invention tempers therapy of atrialfibrillation in a measured and clinically balanced fashion comparable tothe management afforded by expert human cardiac care.

While the invention has been particularly shown and described asreferenced to the embodiments thereof, those skilled in the art willunderstand that the foregoing and other changes in form and detail maybe made therein without departing from the spirit and scope of theinvention.

What is claimed is:
 1. An automated system for diagnosing and monitoringoutcomes of atrial fibrillation, comprising: a database for storing aplurality of monitoring sets which each comprise recorded measuresrelating to patient information recorded on a substantially continuousbasis; a comparison module for receiving a diagnosis of atrialfibrillation and determining at least one patient status change inresponse to the atrial fibrillation diagnosis by comparing on a periodicbasis at least one recorded measure from each of the monitoring sets toat least one other recorded measure from another of the monitoring setswith both recorded measures relating to a same type of patientinformation; and an analysis module for evaluating on a periodic basiseach patient status change for an absence, an onset, a progression, aregression, and a status quo of atrial fibrillation against apredetermined indicator threshold corresponding to the same type ofpatient information as the recorded measures which were compared, theindicator threshold corresponding to a quantifiable physiologicalmeasure of a pathophysiological diagnosis resulting from atrialfibrillation.
 2. An automated system according to claim 1, furthercomprising: an analysis submodule for-managing the atrial fibrillationdiagnosis by controlling at least one of a ventricular rate responsecontrol unit and a normal sinus rhythm restoration unit.
 3. An automatedsystem according to claim 1, further comprising: at least one of amedical device adapted to be implanted in an individual patient and anexternal medical device proximal to the individual patient; a databasesubmodule for periodically receiving the monitoring set for anindividual patient, with each recorded measure in the monitoring setrecorded by the at least one of a medical device adapted to be implantedand the external medical device and storing the received monitoring setin the database as part of a patient care record for the individualpatient.
 4. An automated system according to claim 3, furthercomprising: a set of further indicator thresholds, each indicatorthreshold corresponding to a quantifiable physiological measure used todetect a pathophysiology indicative of diseases other than atrialfibrillation; a comparison submodule for comparing each patient statuschange to each such further indicator threshold corresponding to thesame type of patient information as the at least one recorded measureand the at least one other recorded measure from another of themonitoring sets and for testing each patient status change against eachsuch further indicator threshold corresponding to the same type ofpatient information as the recorded measures which were compared.
 5. Anautomated system according to claim 1, wherein the recorded measurescomprise quality of life measures, further comprising: a comparisonsubmodule for determining a change in patient status by comparing atleast one such recorded quality of life measure to at least one othersuch corresponding recorded quality of life measure.
 6. An automatedsystem according to claim 1, further comprising: a set of stickinessindicators for each type of patient information, each stickinessindicator corresponding to a temporal limit related to a program ofpatient diagnosis or treatment; a comparison submodule for measuring atime occurring between each patient status change for each recordedmeasure to the stickiness indicator relating to the same type of patientinformation as the recorded measure being compared; and an analysissubmodule for determining a revised program of patient diagnosis ortreatment responsive to each patient status change occurring subsequentto the time following the stickiness indicator.
 7. An automated systemaccording to claim 1, further comprising: a database submodule modulefor retrieving the plurality of monitoring sets from a patient carerecord for one of an individual patient, a peer group, and an overallpatient population.
 8. An automated system according to claim 1, furthercomprising: the database for further storing a reference baselinecomprising recorded measures which each relate to patient informationrecorded during an initial time period and comprise either medicaldevice measures or derived measures; and a database submodule obtainingat least one of the at least one recorded measure and the at least oneother recorded measure from the reference baseline.
 9. An automatedsystem according to claim 1, wherein the indicator threshold relates toat least one of a finding of reduced exercise capacity, respiratorydistress, palpitations or symptoms.
 10. An automated system according toclaim 9, wherein the indicator thresholds relating to the finding ofreduced exercise capacity are selected from the group consisting ofdecreased cardiac output, decreased mixed venous oxygen score anddecreased patient activity score.
 11. An automated system according toclaim 9, wherein the indicator thresholds relating to the finding ofrespiratory distress are selected from the group consisting of increasedpulmonary artery diastolic pressure, increased respiratory rate anddecreased transthoracic impedance.
 12. An automated collection andanalysis patient care system for diagnosing and monitoring outcomes ofatrial fibrillation, comprising: a database for storing a plurality ofmonitoring sets, each monitoring set comprising recorded measures whicheach relate to patient information and comprise either medical devicemeasures or derived measures, the medical device measures having beenrecorded on a substantially continuous basis; a set of stored indicatorthresholds, each indicator threshold corresponding to a quantifiablephysiological measure of a pathophysiological diagnosis resulting fromatrial fibrillation and relating to the same type of patient informationas at least one of the recorded measures; and a diagnostic modulediagnosing an atrial fibrillation finding, comprising: an analysismodule for receiving a diagnosis of atrial fibrillation and determiningon a periodic basis a change in patient status in response to the atrialfibrillation diagnosis by comparing at least one recorded measure to atleast one other recorded measure from another of the monitoring setswith both recorded measures relating to the same type of patientinformation; and a comparison module for comparing on a periodic basiseach patient status change for an absence, an onset, a progression, aregression, and a status quo of atrial fibrillation to the storedindicator threshold corresponding to the same type of patientinformation as the recorded measures which were compared.
 13. A systemaccording to claim 12, wherein the device measures are recorded by atleast one of a medical device adapted to be implanted in an individualpatient and an external medical device proximal to the individualpatient when the device measures are recorded.
 14. A system according toclaim 12, wherein each of the monitoring sets comprises recordedmeasures relating to patient information solely for the individualpatient, further comprising: a database module for retrieving eachmonitoring set from a patient care record for an individual patient andfor obtaining the at least one recorded measure and the at least oneother recorded measure from the retrieved monitoring sets.
 15. A systemaccording to claim 12, wherein each of the monitoring sets comprisesrecorded measures relating to patient information for a peer group ofpatients to which the individual patient belongs, further comprising: adatabase module for retrieving at least one monitoring set from apatient care record for the individual patient, for retrieving at leastone other monitoring set from a patient care record in the same patientpeer group, and for obtaining the at least one recorded measure from theat least one monitoring set and the at least one other recorded measurefrom the at least one other monitoring set.
 16. A system according toclaim 12, wherein each of the monitoring sets comprises recordedmeasures relating to patient information for a population of patients,further comprising: a database module for retrieving at least onemonitoring set from a patient care record for the individual patient,for retrieving at least one other monitoring set from a patient carerecord in the patient population, and for obtaining the at least onerecorded measure from the at least one monitoring set and the at leastone other recorded measure from the at least one other monitoring set.17. A system according to claim 12, further comprising: a medical deviceadapted to be implanted; the database for further storing a referencebaseline comprising recorded measures which each relate to patientinformation recorded by the medical device during an initial time periodand comprise either device measures recorded by the medical deviceadapted to be implanted or derived measures; and a database module forobtaining at least one of the at least one recorded measure and the atleast one other recorded measure from the retrieved reference baseline.18. A system according to claim 17, wherein the reference baselinecomprises recorded measures relating to patient information for one ofthe individual patients solely, a peer group of patients to which theindividual patient belongs, and a general population of patients.
 19. Asystem according to claim 12, the comparison module further comprising:a module for grading the comparisons between each patient status changeand corresponding stored indicator threshold on a fixed scale based on adegree of deviation from the stored indicator threshold; and thecomparison module for determining an overall patient status change byperforming a summation over the individual graded comparisons.
 20. Asystem according to claim 12, the comparison module further comprising:a module for determining probabilistic weightings of the comparisonsbetween each patient status change and corresponding stored indicatorthreshold based on a statistical deviation and trends via linear fitsfrom the stored indicator threshold; and the comparison module fordetermining an overall patient status change by performing a summationover the individual graded comparisons.
 21. A system according to claim12, the diagnostic module further comprising: a feedback modulerecording quality of life and symptom measures into each monitoring set;a quality of life module for determining a change in patient status bycomparing at least one recorded quality of life measure to at least oneother corresponding recorded quality of life measure; and the diagnosticmodule for incorporating each patient status change in quality of lifeinto the atrial fibrillation finding to either refute or support thediagnosis.
 22. A system according to claim 12, further comprising: a setof stored further indicator thresholds, each stored further indicatorthreshold corresponding to a quantifiable physiological measure used todetect a pathophysiology indicative of diseases other than atrialfibrillation; and the diagnostic module diagnosing a finding of adisease other than atrial fibrillation, the comparison module furthercomparing each patient status change to each such further indicatorthreshold corresponding to the same type of patient information as theat least one recorded measure and the at least one other recordedmeasure.
 23. A system according to claim 12, further comprising: a setof stickiness indicators, each stickiness indicator corresponding to atemporal limit related to a course of patient care; and a feedbackmodule for comparing a time span between each patient status change foreach recorded measure to the stickiness indicator corresponding to thesame type of patient information as the recorded measure being compared.24. A system according to claim 12, further comprising: a feedbackmodule for providing automated feedback to the individual patient whenan atrial fibrillation finding is diagnosed.
 25. A system according toclaim 24, further comprising: the feedback module for performing aninteractive dialogue between the individual patient and the patient caresystem regarding the individual patient.
 26. An automated patient caresystem for diagnosing and monitoring outcomes of atrial fibrillation,comprising: a database for storing recorded measures organized into amonitoring set for an individual patient with each recorded measurehaving been recorded on a substantially continuous basis and relating toat least one of monitoring reduced exercise capacity and respiratorydistress; a database module for periodically retrieving a plurality ofthe monitoring sets from the database; and a diagnostic module forevaluating at least one of atrial fibrillation onset, progression,regression, and status quo, comprising: a comparison module forreceiving a diagnosis of atrial fibrillation and determining on aperiodic basis a patient status change in response to the atrialfibrillation diagnosis by comparing at least one recorded measure fromeach of the monitoring sets to at least one other recorded measure withboth recorded measures relating to the same type of patient information;and an analysis module for testing on a periodic basis each patientstatus change for an absence, an onset, a progression, a regression, anda status quo of atrial fibrillation against a predetermined indicatorthreshold corresponding to the same type of patient information as therecorded measures which were compared, the predetermined indicatorthreshold corresponding to a quantifiable physiological measure of apathophysiological diagnosis indicative of reduced exercise capacity andrespiratory distress.
 27. An automated system for managing apathophysiological outcome of atrial fibrillation, comprising: adatabase for storing a plurality of monitoring sets from a databasewhich each comprises recorded measures relating to patient informationrecorded on a substantially continuous basis; a comparison module forreceiving a diagnosis of atrial fibrillation and determining on aperiodic basis the pathophysiological outcome of atrial fibrillation inresponse to the atrial fibrillation diagnosis, by comparing at least onerecorded measure from each of the monitoring sets to at least one otherrecorded measure from another of the monitoring sets with both recordedmeasures relating to a same type of patient information and forevaluating on a periodic basis each recorded measure comparison for anabsence, an onset, a progression, a regression, and a status quo ofatrial fibrillation against a predetermined indicator thresholdcorresponding to the same type of patient information as the recordedmeasures which were compared, the indicator threshold corresponding to aquantifiable physiological measure of a pathophysiological diagnosisresulting from atrial fibrillation; and an analysis module for managingthe atrial fibrillation outcome by interventively administering therapycontributing to normal sinus rhythm restoration and ventricular rateresponse control.
 28. An automated system according to claim 27, whereinthe pathophysiological outcome comprises a cardiovascular orcardiopulmonary compromise, further comprising: a comparison submodulefor measuring a magnitude of change and a time span occurrence and forclassifying a severity of the cardiovascular or cardiopulmonarycompromise according to the magnitude of change and the time span foreach recorded measure comparison; and an analysis submodule forgenerating a therapy regimen based on the severity, comprising, indecreasing order of severity: for the cardiovascular or cardiopulmonarycompromise with a highest severity, a submodule administering anaggressive atrial fibrillation therapy; for the cardiovascular orcardiopulmonary compromise of second highest severity, a submoduleadministering initial anticoagulation management coupled with selectiveventricular rate response control for atrial fibrillation of long termduration and administering an aggressive atrial fibrillation therapy inthe presence of anticoagulation drug therapy; for the cardiovascular orcardiopulmonary compromise of third highest severity, a submoduleadministering initial monitored anticoagulation management coupled withselective ventricular rate response control for atrial fibrillation oflong term duration, administering a moderate atrial fibrillation therapycoupled with ventricular rate response control for atrial fibrillationof long term duration and administering a moderate atrial fibrillationtherapy for atrial fibrillation in the absence of anticoagulation drugtherapy; and for the cardiovascular or cardiopulmonary compromise ofleast severity, a submodule administering initial anticoagulationmanagement coupled with selective ventricular rate response control andon-going cardiovascular or cardiopulmonary monitoring for atrialfibrillation of long term duration, administering a modest atrialfibrillation therapy for atrial fibrillation of long term duration andadministering a modest atrial fibrillation therapy for atrialfibrillation in the absence of anticoagulation drug therapy.
 29. Anautomated system according to claim 27, wherein the pathophysiologicaloutcome comprises an inappropriate ventricular rate response, farthercomprising: a comparison submodule for measuring an average ventricularrate and for classifying ventricular rate response according to theaverage ventricular rate; and an analysis submodule for generating atherapy regimen based on the severity, comprising: for overly slowventricular rate response, a submodule performing at least one therapyselected from the group comprising increasing ventricular pacing rateand decreasing antidromotropic drug therapy; and for overly rapidventricular rate response, a submodule performing at least one therapyselected from the group comprising applying electrical therapy andadministering initial drug therapy to decrease atrioventricular nodeconduction.
 30. An automated system according to claim 27, wherein (hepathophysiological outcome comprises a pathophysiological conditionrequiring anticoagulation drug therapy, further comprising: a comparisonsubmodule for determining a duration for atrial fibrillation andanticoagulation drug therapy status; and an analysis submodule foradministering anticoagulation drug therapy for atrial fibrillation oflong term duration in the absence of a contraindication ofanticoagulation drug therapy or inadequacy thereof.
 31. An automatedsystem according to claim 27, wherein the pathophysiological outcomecomprises palpitations or symptoms, further comprising: a comparisonsubmodule for classifying palpitations or symptoms according todisabling effect to the patient; and an analysis submodule forgenerating a therapy regimen based on the classification, comprising:for disabling palpitations or symptoms, a submodule administering amoderate atrial fibrillation therapy for atrial fibrillation; and fornon-disabling palpitations or symptoms, a submodule administering amodest atrial fibrillation therapy for atrial fibrillation.